CAI is now actively under investigation in 4 clinical trials at NCI and through CTEP. Our phase I study of daily CAI with 3 weekly paclitaxel is in its 5th dose escalation level, without dose limiting toxicity. Clinical benefit has been seen in cervical cancer, ovarian cancer, renal cancer, and pancreatic cancer. No new side effects have been identified in this schedule. While it was found that paclitaxel stimulated a rise in circulating CAI concentrations in a paclitaxel dose-dependent fashion in the intermittent CAI/paclitaxel schedule, no evidence of a sustained rise or cumulative rise in CAI concentrations have been observed to date in the continuous CAI arm. The phase II pharmacokinetically dosed ovarian cancer phase II study has accrued 28 pts to date. Over 35% of patients have attained disease stabilization for 6 months or longer. It was recently found that CAI reduced circulating concentrations of human IL-8 and human VEGF in a murine melanoma xenograft model. Thus, blood is being stored for measurement of circulating VEGF, and IL-8, and MMP-2 concentrations. Analysis of 6 patients to date shows that in one patient MMP-2 concentration varied in parallel with the patient's clinical status, and in another patient, both VEGF and IL-8 increased as disease began to grow and metastasize. CA125 values do not tightly mirror objective clinical assessment of disease by CT and physical examination in this study cohort. Collaboration continues investigating the application of CAI for ophthalmologic use. Excellent scleral permeability has been found in ex vivo models and it has been shown to be problematic when used in implant form due to hygroscopicity altering release over time. No direct ocular toxicity has been identified to date in the rabbit models with implants and the screening observations in the patients on the phase II trial have yielded no drug-related ophthalmologic toxicity